The Oswestry Metabolic BONE Cohort

NCT07014306 | Not Yet Recruiting

• 1 other identifier: RL1 899
• Study Type: observational
• Target: 4,200
• Locations: 1 country
• Sites: 1

Brief Summary

Osteoporosis is a chronic condition characterised by reduced bone mass and microarchitectural deterioration of bone tissue leading to fracture. One in two adult women and one in five men will sustain a fragility fracture in their lifetime. The fractures caused by osteoporosis are a leading cause of morbidity and mortality. Optimising bone health and prevention of fracture is the best management strategy and requires detection and correction of any risk factors associated with fracture. Multiple studies have established clinical risk factors associated with fracture, including low bone mineral density (BMD), lifestyle factors such as smoking and excessive alcohol intake, a parental history of hip fracture, and glucocorticoid use, among others. The incorporation of these clinical risk factors with BMD using the well validated Fracture Risk Assessment Tool (FRAX) over the last two decades has significantly improved fracture risk prediction. Nonetheless, BMD and FRAX have limitations, and many patients continue to experience fractures despite having normal or elevated BMD and no identifiable FRAX elements. Additionally, FRAX does not utilise any biomarkers, many of which may have a significant role in fracture risk. Beyond the traditional well-established clinical risk factors incorporated into FRAX, new comorbidities have emerged in recent years as important determinants of bone strength and susceptibility to fracture. Obesity, type II diabetes, sarcopenia (age related progressive loss of muscle tissue), and frailty are global pandemics and have been increasingly linked with fracture risk. On the case of obesity, for example, there has been an increasing debate whether obese patients are at higher or lower risk for fracture. Whilst Body Mass Index (BMI) remains the most widely used measure of obesity, BMI is not a direct measurement of central obesity which is better assessed by waist circumference, percentage body fat measured by whole body areal bone mineral density (BMD), or visceral fat area measured by computed tomography (CT). In 2023, the National Institute for Health and Care Excellence (NICE) recommended the measurement of waist to height ratio (WHtR) as a practical estimate of central adiposity with a ratio of ≥ 0.6 as a cut-off for high central adiposity. Waist circumference was introduced in the metabolic bone unit at the Robert Jones and Agnes Hunt Orthopaedic Hospital (RJAH) as a routine clinical measurement in 2023 following NICE recommendation. In addition to obesity, clinical frailty measured by the Rockwood Clinical Frailty Scale, sarcopenia which is a state of reduced muscle power and declined muscle function, and type 2 diabetes are all variables that can be easily collected in routine clinical practice and are likely to play significant roles in numerous health outcomes including ageing, fracture, and mortality. Along with routine measurements, taken as standard of care, we also plan to utilise some of the latest scientific techniques and research into metabolomics and microbiome studies in subgroups of our patients. Further research is urgently needed in these areas to further the osteoporosis field and benefit patients at risk of fracture. The metabolic bone service at RJAH is one of the largest metabolic services in the UK in terms of patient numbers and our service continues to experience a significant growth in demand. We have a considerable amount of data collected from patients attending the metabolic clinic and bone density unit over many years. We have a track record of successfully using patient data, anonymously, to enhance our knowledge of bone health and the risk factors of fracture to optimise treatment for our patients through well designed research studies. We have previously assessed the use of bone markers for monitoring treatment, found relationships between levels of hormone therapy and bone density, levels of hormones on bone markers and serious side effects of bisphosphonate treatment.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (2)

• Cohort 1 Time to fracture

  Time to subsequent fracture following baseline assessment.

  5 years

• Cohort 1 cumulative fracture

  Cumulative risk of fracture at 2 and 5 years.

  5 years

Secondary Outcomes (10)

• Cohort 2 Change in BMD

  5 years

• Cohort 2 fracture at different sites

  5 years

• Cohort 2 BMI and WHtR for fracture prediction

  5 years

• Cohort 2 Difference in healthcare resource for obese and non-obese patients

  10 years

• Predictive values of biomarkers in fracture risk

  10 years

Study Arms (2)

Cohort 1: Bone health clinical cohort Suitable patients attending our service for a DXA scan in 2025

GP records will be accessed in consenting patients to gain complete and up-to-date medical history, especially information on diagnoses including fracture, diabetes, height, weight, smoking, alcohol intake as well as previous and current medications. As all of this information impacts on the treatment plan for a patient, it is vital that it is accurately obtained. A group of patients will also be asked about their willingness to be involved in PPIE activities and taking part in future clinical trials. We aim to use this data to discover new trends and relationships pertaining to bone health which will allow us to further extend our studies, improve our knowledge and ultimately benefit patients.

Cohort 2: Exploratory cohort of 'omics', microbiome, bone structure, and body composition.

The main objectives are to assess the following: * Omics biomarkers and their predictive values on bone health outcomes, sarcopenia, frailty, ageing, and response to osteoporosis treatments. * Body composition (lean mass and fat mass) measured by whole body DXA. * Quantitative fat assessment measured by MRI of muscle and bone marrow with a focus on visceral fat/intramuscular fat/ sub cutaneous fat. * Bone microstructure measured by QCT at tibia, wrist, hip, and/or spine. * Microbiome studies from stool, urine, blood and or saliva samples.

Diagnostic Test: MRI; Diagnostic Test: Computed tomography

Interventions

MRI DIAGNOSTIC_TEST

Cohort 2

Cohort 2: Exploratory cohort of 'omics', microbiome, bone structure, and body composition.

Computed tomography DIAGNOSTIC_TEST

Quantitative computed tomography

Cohort 2: Exploratory cohort of 'omics', microbiome, bone structure, and body composition.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

From patients attending the metabolic bone service at the RJAH.

You may qualify if:

• A fragility fracture sustained during two years prior to the baseline DXA including spine, hip, wrist, humerus, pelvis, elbow, rib, sternum, clavicle, scapula, distal femur, tibia, fibula, and foot
• A DXA measurement at the lumbar spine and hip between 2025-2035
• Non-osteoporotic BMD (T-score \>-2.5) and
• Anti-osteoporosis therapy not recommended following the DXA scan

You may not qualify if:

• Traumatic fracture
• Patients who lack capacity.

Sponsors & Collaborators

• Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust: lead

Study Sites (1)

The Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Foundation Trust

Oswestry, Shropshire, SY10 7AG, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, saliva, stool.

MeSH Terms

Conditions

Osteoporosis

Interventions

Tomography, X-Ray Computed

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Central Study Contacts

Claire Dr Mennan, PhD

CONTACT

01691 404699; claire.mennan@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: June 10, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2035
• Study Completion (Estimated): June 1, 2035
• Last Updated: June 10, 2025

Record last verified: 2025-06

Locations

GB (1)